The present invention relates to the use of the unsaponifiable components of vegetable oils, in particular of avocado, soya bean and/or lupin oils, for the preparation of a medicament stimulating the expression of TGF-β or the expression of the plasminogen activator inhibitor PAT-1, as well as a method of cosmetic treatment according to which a composition based on unsaponifiable component of vegetable oils is applied to the skin, the neighbouring mucous membranes and/or the superficial body growths.
“TGF-β” is understood to mean, according to the invention, the different isoforms of TGF-β, that is to say the isoforms of the transforming growth factor β. The isoforms of TGF-β constitute a family of homodimeric polypeptides having a molecular weight of about 25 kD. Among the 5 known isoforms, the best characterized are the TGF-β1 and TGF-β2 (Sporn et al. (1987), J. Cell Biol. 105, 1039-1045; Roberts and Sporn (1990), Handbook of Exp. Pharmacol. 35, 419-472, Springer Verlag, Heidelberg). Although these two isoforms exhibit only 71% homology, they appear to have many activities in common. TGF-β1 was first isolated from human platelets, but it is now known that the majority of cells are capable of expressing it. TGF-β2 was purified from platelets, from bovine bone and from glyoblastoma cells.
It is known that TGF-β is involved in complex mechanisms of progression of various pathologies and that it is desirable to reinforce the action of TGF-β, in other words to increase its expression by the very cells involved in the mechanisms of the said pathologies, for a favourable progression of the latter.
Thus, for example, it is known that the TGF-β expressed by the articular chondrocytes is involved in anabolic mechanisms of reaction, that is to say of restoration, of the articular cartilage which are observed at the first stages of osteoarthritis and which tend to compensate for the degradation of the cartilage resulting from the activity of metalloproteases which are excessively secreted by the chondrocytes under the effect of cytokines, such as interleukin-1 (IL-1). It would therefore be desirable, for example in the case of osteoarthritis, to slow down the progression of this disease not only by blocking the activity of interleukin-1 by known means but also by promoting the expression of TGF-β.
Moreover, it is known that TGF-β is favourably involved in the mechanisms of bone remodelling which occur during osteoporosis. This has been shown in particular by Boyce et al. of the University of Texas ((1996), Nature Med. (2), 10, 1132-1136).
Finally, TGF-β also plays a favourable role in some mechanisms of differentiation of nerve cells which are induced by the nerve growth factor (NGF or “nerve growth factor”) as well as in many aspects of tissue, in particular skin, repair.
Taking into account the preceding text, it was therefore highly desirable to be able to obtain a stimulatory effect on the expression of TGF-β, in particular in order to improve the treatment of the pathologies described above.
Moreover, “plasminogen activator inhibitor 25 PAI-1” is understood to mean, according to the invention, the specific inhibitor PAI-1 which, with the other inhibitor PAI-2, regulates, in a known manner, the activity of the tissue form (tPA) and of the urokinase type (uPA) of the plasminogen activator PA. The two forms of PA, tPA and uPA, are produced by two different genes and have different molecular weights and immunological reactivity (Dano et al., (1985) Adv. Cancer Res. 44, 139-166; Hart et al., (1988), Comp. Bioch. Physiol. 90 B, 691-708). The inhibitors PAI-1 and PAI-2 form stable complexes with tPA and uPA. PAI-1 is the form which is predominant in the plasma and is produced by the endothelial cells, the platelets and the cells of the joint such as the synovial cells and the chondrocytas (Hart et al., 1988; Campbell et al., 1991; Hamilton et al., 1992).
It would be particularly advantageous to be able to stimulate the expression of the plasminogen activator inhibitor PAI-1 since an inhibition of the action of the metalloproteases and therefore, in particular, a contribution to the action of TGF-β for a favourable progression of the abovementioned pathologies would thus be obtained.